Optically active epoxides and a process for the production thereof

ABSTRACT

The present invention is optically active epoxides and its production characterized in that the process comprises reacting alkenyl ethylene glycols with 0.5 to 2.0 equivalents of a titanium-tetraalkoxyde, a peroxide and an L-(+)- or D-(-)-dialkyl tartrate at a temperature of -78° to 50° C. to asymmetrically oxidize the alkenyl ethylene glycols. The production of the present invention is an excellent method for producing chiral epoxides in which steric configuration of three asymmetric points can be perfectly controlled, the reaction is performed by mild conditions and the chemical yield and the optical yield are extremely high. The optically active epoxides which can be efficiently produced by the production of the present invention are useful as stating materials of several kinds of compounds.

This is a division of application Ser. No. 07/885,795 filed May 20,1992, now U.S. Pat. No. 5,254,704.

BACKGROUND OF THE INVENTION

The present invention related to a process for the production ofoptically active compounds, characterized in that it comprises oxidizingstereoselectively alkenyl ethyleneglycols, and to the optically activecompounds which are advantageously obtained by the method and utilizableas starting materials of physiologically active compounds.

Generally, when the physiologically active compounds have asymmetriccarbons, there are plural stereoisomers. Usually, only a stereoisomeramong these stereoisomers shows advantageous characteristics. When astereoisomer which is a racemate or a steroisomer having low opticalpurity is used, it is apparent that the resulting compounds does notsufficiently exhibit physiological activity.

Optically active compounds which can be produced by the process of thepresent invention are fully controlled in the steric configuration ofthree asymmetric positions. Although it is considered that the compoundsare useful for raw materials of various useful physiological activecompounds, a process for efficiently producing the compounds is stillunknown from the complexity of the structure. As an example, ##STR1##(E.J. Corey et al., J. Am. Chem. Soc. 102(27), 7984 (1980)) and ##STR2##(J. Rokach et al., Prostaglandins, 1, 65(1981)) are known asintermediates for synthesizing leukotrienes. However, only a process forproducing the compounds via several steps from mannose which is a sugaris described, but a process for efficiently producing the compounds isstill unknown.

SUMMARY OF THE INVENTION

An object of the present invention is to efficiently provide opticallyactive compounds having high optical purity which are useful forstarting materials of physiologically active compounds.

The inventors of the present invention conducted research for attainingthe above object, found that particular optically active epoxides havinghigh optical purity are efficiently obtained by oxidation reaction ofspecial alkenyl ethylene glycols used as starting materials, and thenbrought the present invention to completion.

Namely, the present invention provides a process for the production ofan optically active epoxide represented by the general formula: ##STR3##wherein R is a hydrocarbon group of 40 or less carbon atoms and it maycontain at least an oxygen, a nitrogen or a sulfur, which comprisesreacting an alkenyl ethylene glycol represented by the general formula:##STR4## wherein R is the same as that described above, with 0.5 to 2.0equivalents of a titanium-tetraalkoxyde, a peroxide and an L-(+)- orD-(-)-dialkyl tartrate at a temperature of -78° to 50° C. toasymmetrically oxidize the alkenyl ethylene glycol.

DETAILED DESCRIPTION OF THE INVENTION

In the process, titanium tetraisopropoxide is preferably used as thetitanium tetralkoxyde.

Furthermore, t-butylhydroperoxide is preferably used as the peroxide.

Moreover, disopropyl tartrate is preferably used as the dialkyltartrate.

In addition, the present invention is an optically active epoxiderepresented by the formula: ##STR5##

Further, the present invention is an optically active epoxiderepresented by the formula: ##STR6##

Further, the present invention is an optically active epoxiderepresented by the formula: ##STR7##

Moreover, the present invention is an optically active epoxiderepresented by the formula: ##STR8##

Furthermore, the present invention is an optically active epoxiderepresented by the formula: ##STR9##

Furthermore, the present invention is an optically active epoxiderepresented by the formula: ##STR10##

The following description illustrates the present invention morespecifically. The process of the present invention is provided by thefollowing steps.

Namely, an optically active compound represented by the formula (2) isproduced by reacting an alkenyl ethyleneglycol represented by theformula (1) with 0.5 to 2.0 equivalent of a titanium tetraalkoxyde, aperoxide and an L-(+)- or D-(-)-dialkyl tartrate at a temperature of-78° to 50° C., preferably -20° C. under anhydrous conditions toasymmetrically oxidize the alkenyl ethyleneglycol. When the amount ofthe titanium tetraalkoxyde and the like is less than 1.0 equivalent, thechemical yield of the resulting compound is undesirably too low. Whenthe amount is more than 2.0 equivalent, it is unpreferable because theremoval operation of the titanium tetraalkoxide and peroxide becomestroublesome. Further, when the temperature is too low, the reactionhardly proceeds. When the temperature is too high, the steroselectivityunpreferably becomes low.

As the titanium tetraalkoxyde, peroxide and L-(+)- or D-(-)-dialkyltartrate, industrially available titanium tetraisopropoxide, t-butylhydroperoxide (abbreviated as TBHP hereinafter), L-(+)- orD-(-)-diisopropyl tartrate (abbreviated as L-(+)- or D-(-)-DIPThereinafter) can be used without any trouble.

The dehydration from the reaction system is conducted with sufficientefficiency by using molecular sieves. Any kind of dehydrating agentshaving dehydrating ability can be used. In addition, any kind ofnonaqueous solvents can be used in the reaction system. Dichloromethaneis particularly preferred. ##STR11##

(In the above formula, R is the same as that described above.)

Further, when the compound represented by the formula (1') in thealkenyl ethylene glycol represented by the formula (1) is used as astarting material, the compound represented by the formula (2') can beobtained by using L-(+)-DIPT, while the compound represented by theformula (2") can be obtained by using formula (1") and D-(-)-DIPT.##STR12## (In the above formula, R is the same as that described above.)

Starting material alkenyl ethylene glycols represented by the formula(1) can be easily produced by using allyl alcohol (13) as a raw materialwhich is easily derived from isopropylidene glycerol (11) orepichlorohydrin (12) industrially available at a low cost. Namely, thecompound represented by the formula (14) is produced by chlorinatingallyl alcohol represented by the formula (13) with methanesulfonylchloride in the presence of pyridine, and then the resulting compound isreacted with a Grignard reagent in the present of copper (I) iodide toproduce the compound represented by the formula (1'):

Further, the compound represented by the formula (15) is produced byacetylating allyl alcohol represented by the formula (13) with aceticanhydride in the presence of pyridine and 4-dimethylaminopyridine(DMAP), and then the resulting compound is reacted with a lithiumreagent in the presence of copper (I) iodide to produce the compoundrepresented by the formula (1'): ##STR13## (In the above formula, R', R"and R"' indicates the same or different alkyl groups.)

Then, the compound represented by the formula (16) is obtained byetherifying allyl alcohol represented by the formula (13) with a halide.The resulting compound is treated with an acid to obtain the compoundcontaining oxygens represented by the formula (1'a). Further, thecompound represented by the formula (17) is obtained by reacting thecompound represented by the formula (14) with an amine, acetone isremoving from the resulting compound, and the compound containing anitrogen atom represented by the formula (1'b) is produced.

Using compounds having opposite configuration to the compoundsrepresented by the formulas (11) and (12) as starting materials,compounds having opposite configuration to the compounds represented bythe formulas (1'), (1'a) and (1'b) can be obtained.

The production process of the present invention is applicable to anykind of alkenyl ethyleneglycols. These compounds can be changed tocorresponding optically active epoxides represented by the formula (2)having high optical yields and high optical purities. An example isshown in Table 1.

                  TABLE 1                                                         ______________________________________                                                                  Yield   Optical                                     Exp. Compound             (%)     purity (% ee)                               ______________________________________                                              ##STR14##           92      89                                          2                                                                                   ##STR15##           77      99                                          3                                                                                   ##STR16##           73      85                                          4                                                                                   ##STR17##           87      --                                          5                                                                                   ##STR18##           56      --                                          6                                                                                   ##STR19##           63      100                                         ______________________________________                                    

DESCRIPTION OF PREFERRED EMBODIMENTS

The following examples illustrate the invention more specifically.##STR20##

The optical purity of the optically active compound represented by theformula (2') obtained by the process of the present invention iscalculated by comparing a reference value of optical purity of a knowncompound with the specific rotation of epoxyalcohols represented by theformula (18) which is obtained by oxidation with periodic acid followedby reducing with sodium borohydride.

EXAMPLE 1 ##STR21##

Production of the optically active epoxide represented by the formula(3) (in the formula (2), a compound wherein R is a benzyloxy group).

1st step

To 20 ml of suspension of 1.08g (22.4 mmol) of sodium hydride in DMF,3.0 g (18.7 mmol) of allyl alcohol represented by the formula (13) in 3ml of DMF was added dropwise on ice cooling and the resulting mixturewas stirred for 30 min. Then, 2.6 ml (21.5 mmol) of benzyl bromide wasadded dropwise to the solution and the mixture was further stirred for 8hours. After adding water, the mixture was extracted with diethyl ether.The organic layer was washed with brine and dried on anhydrous magnesiumsulfate and concentrated under reduced pressure. The residue waspurified by silica gel chromatography, and 3.28 g (70%) of benzyletherrepresented by the formula (16a) was obtained.

[α]_(D) ²⁸ +24.4 (c2.02,CHC1₃),

IR(neat):1454, 1371, 1061 cm⁻¹,

¹ H-NMR δ:7.33 (s, 5H), 6.10-5.50(m,2H), 4.52(s,2H), 4.65-4.40(m,1H),4.20-3.95(m, 3H), 3.60(t, 1H, J=7.8Hz), 1.43(s, 3H), 1.40(s, 3H),

MS m/e:247, 91

2nd step

The mixture of 3.2g (12,8 mmol) of benzylether represented by theformula (16a) obtained in 1st step, 5ml of 5% hydrochloric acid and 15ml of methanol was stirred at room temperature for 3 hours. The mixturewas neutralized with sodium bicarbonate and concentrated under reducedpressure. The residue was dissolved in dichloromethane. The solution wasdried on anhydrous magnesium sulfate and concentrated under reducedpressure. The residue was purified by silica gel chromatography, and2.55g (96%) of 4.5-dihydroxy-2-pentenylbenzylether represented by theformula (1a) was obtained.

[α]_(D) ²⁷ +4.4°(c 1.34, CHC1₃),

IR(neat):3370, 1451, 1067 cm⁻¹,

¹ H-NMR δ:7.33 (s, 5H), 6.10-5.60 (m, 2H), 4.52(s, 2H), 4.35-4.10(m,1H), 4.00 (brs, 2H, J=4Hz), 3.70-3.30 (m, 2H), 2.65(brs, 2H),

MS m/e:208, 91

3rd step

To 20 ml suspension of 1 g of ground dry molecular-sieves 4A (MS-4A) in20 ml of dichloromethane, 0.75 ml (2.52 mmol) of titaniumtetraisopropoxide, 675 mg (2.88 mmol) of L-(+)-DIPT in 3 ml ofdichloromethane were added at -20° C. The mixture was stirred for 30minutes. To the mixture, 3 ml of a solution of 500 mg (2.4 mmol) of4,5-dihydroxy-2-pentenylbenzylether represented by the formula (1a)obtained in (2nd step) in dichloromethane was added. The mixture wasstirred for one hour and 1.5 ml (2.64 mmol) of 1.8M-TBHP dichloromethanesolution was added dropwise. The mixture was stirred at -20° C. for 80hours. To the mixture, 5 ml of water and 25 ml of acetone were added andstirred at room temperature. The mixture was filtered with cerite, andthe filtrate was concentrated. The residue was purified by silica gelchromatography and 495 mg (92%) of the optically active epoxiderepresented by the formula (3) was obtained.

[α]_(D) ²⁵ -11.0°(c 1.01, CHC1₃),

IR (neat): 3400cm⁻¹,

¹ H-NMR δ:7.33(m, 5H), 4.56(s, 2H), 3.80-3.35(m, 5H), 3.20(m,1H),3.05(brm, 1H), 2.80(brs, 1H), 2.50(brs, 1H),

MS m/e:224, 107.

4th step

To the mixture of 100 mg (0.45 mmol) of optically active epoxide of theformula (3) obtained in 3rd step, 1 ml of a saturated aqueous sodiumbicarbonate, 1 ml of water and 2 ml of methanol, 210 mg (0.98 mmol) ofsodium periodate was added on ice cooling. The mixture was stirred for 3hours and 37 mg (0.98 mmol) of sodium borohydride was added. The mixturewas stirred for 30 minutes and extracted with dichloromethan, and thedichloromethane solution was dried on anhydrous magnesium sulfate andconcentrated under reduced pressure. The residue was purified by silicagel chromatography and 58 mg (67%) of the compound represented by theformula (18a) was obtained. The optical purity of the resulting compoundwas about 89%ee by comparing with specific rotation of reference value.

[α]_(D) ²⁶ -18.6°(c 1.6, CHC1₃),

(Reference value, [α]_(D) ²⁵ -21°(c 0.97, CHC1₃),

P. MA et al., J. Org. chem., 47, 1378 (1982)).

EXAMPLE 2 ##STR22##

Production of the optically active epoxide represented by the formula(4) (a compound of the formula (2) wherein R is anN-benzyl-p-toluenesulfonamide group).

1st step

To the mixture of 3.0 g (19 mmol) of allyl alcohol represented by theformula (13), 2.3 ml (28.5 mmol) of pyridine and 40 ml ofdichloromethane, 1.8 ml (22.8 mmol) of methanesulfony chloride was addedand stirred at room temperature for 48 hours. The reaction mixture wasextracted with dichloromethane and dried on anhydrous magnesium sulfateand concentrated under reduced pressure. The residue was purified bysilica gel chromatography and 1.95 g (58%) of a chloride represented bythe formula (14) was obtained.

¹ H-NMR δ:6.15-5.60(m, 2H), 4.65-4.40(m, 1H), 4.10(dd, 1H, J=6.3,8.3Hz), 4.05(d, 2H, J=5.4Hz), 3.60(dd, 1H, J=6.9, 6.3Hz), 1.68(s, 3H),1.40(s, 3H),

MS m/e:177, 161, 43

2nd step

500 mg (2.8 mmol) of the chloride represented by the formula (14)obtained in (1st Step) and a solution of 1.2 ml (11.2 mmol) ofbenzylamine in 5 ml of toluene were stirred for 48 hours at atemperature of 80° C. The solvent was distilled away under reducedpressure. To the residue, 1.2 ml (8.4 mmol) of triethylamine, 20 ml ofdichloromethane and 1.33 g (6.0 mmol) of p-toluenesulfonyl chloride wereadded on ice cooling. The mixture was stirred at room temperature for 10hours. After the mixture was stirred by adding water anddichloromethane, organic layer was washed with water and dried onanhydrous magnesium sulfate and concentrated under reduced pressure toobtain 2.12 g of crude sulfonamide. A mixture of 2.12 g of the resultingsulfonamide, 3 ml of 5% hydrochloric acid and 10 ml of methanol wasstirred at room temperature for 5 hours, and then neutralized by addingsodium hydrogencarbonate. After extracting the reaction mixture withdichloromethane, the extract was dried on anhydrous magnesium sulfateand concentrated under reduced pressure, the residue was purified bysilica gel chromatography and 822 mg (78%) of anN-benzyl-p-toluenesulfonamide compound represented by the formula (1b)was obtained.

[α]_(D) ²⁷ +3.4°(c 1.07, CHC1₃),

IR (neat):3400cm⁻¹,

¹ H-NMR δ:7.80-7.60(brd, 2H, J=8.2Hz), 7.5-7.20(brm, 7H), 6.10-5.60(m,2H), 4.35(brs, 2H), 3.90-2.90(m, 7H), 2.45(brs, 3H), MS m/e:343, 91.

3rd Step

To a suspension of 400 mg of ground dry molecular sieves 4A(MS-4A) in 10ml of dichloromethane, a solution of 0.23 ml (0.76 mmol) of titaniumtetraisopropoxide and 205 mg (0.86mmol) of L-(+)-DIPT in 3ml ofdichloromethane were added at -20° C. The mixture was stirred for 30minutes. A solution of 260 mg (0.72 mmol) of theN-benzyl-p-toluenesulfonamide compound obtained in (2nd Step) in 3 ml ofdichloromethane was added to the mixture, and the mixture was stirredfor 1 hour. After 0.6 ml (1.08 mmol) of 1.8M-TBHP dichloromethanesolution was added dropwise, the mixture was stirred for 72 hours at-20° C. 3 ml of water and 15 ml of acetone were added, and the mixturewas stirred at room temperature. After filtrating the mixture withcerite, the filtrate was concentrated. The residue was purified bysilica gel chromatography and 210 mg (77%) of the optically activeepoxide represented by the fomula (4) was obtained.

[α]_(D) ²⁸ -22.6°(c 1.01, CHC1₃),

IR (neat):3420, 1340, 1155cm⁻¹,

¹ H-NMR δ:7.70(brd, 2H, J=8.2Hz), 7.50-7.20(brm, 7H), 4.35(brs, 2H),3.70-3.50(brm, 2H), 3.50-3.20(m, 1H), 3.20-3.00(m, 2H), 3.00-2.80(m,1H), 2.70-2.30(m, 3H), 2.44(brs, 3H),

MS m/e:378, 346, 222, 91.

4th Step

To a mixture of 165 mg (0.44 mmol) of the optically active epoxiderepresented by the formula (4) obtained in (3rd Step), 1 ml of saturatedaqueous sodium bicarbonate, 1 ml of water and 2 ml of methanol, 224 mg(1.06 mmol) of sodium periodate was added on ice cooling. After themixture was stirred for 3 hours, 40 mg (1.06 mmol) of sodium borohydridewas added and the mixture was stirred for 30 minutes. The reactionmixture was extracted with dichloromethane and the extract was dried onanhydrous sodium sulfate. The solvent was distilled away under reducedpressure. The residue was purified by silica gel chromatography toobtain 135 mg (88%) of the hydroxy epoxide represented by the formula(18b). It was found that the optical purity of the optically activeepoxide represented by the formula (4) was about 99%ee by comparing witha specific rotation of the reference value.

[α]_(D) ²⁷ -19.9°(c 1.96, CHC1₃),

(Reference value, enantiomer [α]_(D) ²⁰ +20.0°(c 1.84, CHC1₃),

C.E. Adams et al., J. Org. Chem., 50, 420 (1985)).

EXAMPLE 3 ##STR23##

Production of the optically active compound represented by the formula(5) (a compound of the formula (2) wherein R is a n-butyl group)

1st step

To a mixture of 700 mg (4.4 mmol) of the allyl alcohol represented bythe formula (13), 0.8 ml (9.86 mmol) of pyridine, 109 mg (0.88 mmol) of4-DMAP and 20 ml of dichloromethane, 0.84 ml (8.9 mmol) of aceticanhydride was added dropwise on ice cooling and the mixture was stirredfor 3 hours at a room temperature. The reaction mixture was extractedwith dichloromethane, the extract was washed with a saturated aqueoussodium hydrogencarbonate and dried on anhydrous magnesium sulfate, andconcentrated under reduced pressure. The residue was purified by silicagel chromatography to obtain 660 mg (75%) of the allyl acetaterepresented by the formula (15).

IR (neat):1741, 1372 cm⁻¹,

¹ H-NMR δ:6.10-5.50(m, 2H), 4.55(d, 2H, J=4.4Hz), 4.60-4.40(m,1H),4.10(dd, 1H, J=6.1, 8.0Hz), 3.65(t, 1H, J=8.2Hz), 2.07(s, 3H), 1.43(s,3H), 1.40(s, 3H),

MS m/e:201, 185, 43.

2nd step

To 25 ml of a diethylether solution of 726 mg (3.81 mmol) of copper (I)iodide, 4.8 ml (7.62 mmol) of 1.6M-butyllithium hexane solution wasadded dropwise, and the mixture was stirred at 0° C. for 15 minutes.After the mixture was cooled to -30° C., a solution of 635 mg (3.18mmol) of the allyl acetate represented by the formula (15) obtained in(1st Step) in 3 ml of THF was added dropwise, and the mixture wasstirred for 1 hour. After a saturated aqueous ammonium chloride wasadded, the mixture was warmed to room temperature and extracted withdiethyl ether. The extract was washed with a saturated aqueous sodiumbicarbonate and then with brine. After the extract was dried onanhydrous magnesium sulfate, the solvent was distilled away underreduced pressure and 680 mg of crude acetonide was obtained as theresidue. A mixture of 300 mg (1.5 mmol) of the crude acetonide, 2 ml of5% hydrochloric acid and 5 ml of methanol was stirred at roomtemperature for 3 hours. After the mixture was neutralized with sodiumbicarbonate, it was concentrated under reduced pressure, and the residuewas dissolved in dichloromethane. The solution was dried on anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas purified by silica gel chromatography to obtain 156 mg (66%) of 1,2-dihydroxy-3-nonene represented by the formula (1c).

[α]_(D) ²⁸ +17.1°(c 1.03, CHC1₃),

IR (neat):3360, 1074 cm⁻¹,

¹ H-NMR δ:5.80(td, 1H, J=5.3, 16.0Hz), 5.45(dd, 1H, J=5.0, 16.0Hz),4.30-4.00(brm, 1H), 3.70-3.30(m,2H), 2.45(brs, 2H), 2,00(brt, 2H,J=5.5Hz), 1.50-1.00(brs, 6H), 0.80(t, 3H, J=7.3Hz),

MS m/e:158, 127, 57.

3rd step

To a suspension of 600 mg of ground dry molecular sieves 4A(MS-4a) in 10ml of dichloromethane, a solution of 0.44 ml (1.20 mmol) of titaniumtetraisopropoxide, 395 mg (1.68 mmol) of L-(+)-DIPT in 3 ml ofdichloromethane was added at -20° C., and the mixture was stirred for 30minutes. A solution of 180 mg (1.14 mmol) of 1, 2-dihydroxy-3-nonenerepresented by the formula (1c) obtained in (2nd Step) in 3 ml ofdichloromethane was added to the mixture. After the mixture was stirredfor 1 hour, 0.76 ml (1.68 mmol) of 1.8M-TBHP dichlomethane solution wasadded dropwise, and the mixture was stirred at -20° C. for 72 hours.After adding 2 ml of water and 10 ml of acetone, the mixture was stirredat room temperature. After the mixture was filtered with celite and thefiltrate was concentrated. The residue was purified by silica gelchromatography and 145 mg (73%) of the optically active epoxiderepresented by the formula (5) was obtained.

[α]_(D) ²⁷ -19.2°(c 1.02, CHC1₃),

IR (neat):3350cm⁻¹,

¹ H-NMR δ:3.70(brs, 3H), 3.20-2.65(m, 4H), 1.70-1.00(m, 8H), 0.80(t, 3H,J=7.5Hz),

MS m/e:175, 143, 55.

4th Step

To a mixture of 100 mg (0.57 mmol) of optically active epoxiderepresented by the formula (5) obtained in (3rd Step), 1 ml of asaturated aqueous sodium bicarbonate, 1 ml of water and 2 ml ofmethanol, 292 mg (1.36 mmol) of sodium periodate was added on icecooling. After the mixture was stirred for 3 hours, 73 mg (1.84 mmol) ofsodium borohydride was added and the mixture was stirred for 30 minutes.After the reaction mixture was extracted with dichloromethane and theextract was dried on anhydrous sodium sulfate. The solvent was distilledaway under reduced pressure. The residue was purified by silica gelchromatography to obtain 70 mg (82%) of 1-hydroxy-2, 3-epoxyoctene(18c). It was found that the optical purity of the optically activeepoxide represented by the formula (5) was about 85%ee by comparing withspecific rotation of the reference value.

[≢]_(D) ²⁷ -37.9°(c 14, CHC1₃),

Reference value [α]_(D) -44.4°(c 0.49, CHC1₃),

S. Takana et al., J. Chem. Soc, Chem. Commun., 1344 (1989)).

EXAMPLE 4 ##STR24##

Production of the optically active epoxide represented by the formula(6) (a compound of the formula (2) wherein R is a phenyl group)

1st step

To 35 ml of a solution of 3.03 mg (15.9 mmol) of copper (I) iodide indiethyl ether, 16 ml (31.8 mmol) of a 2.0M-phennyl lithium hexanesolution was added dropwise, and the mixture was stirred at 0° C. for 15minutes. The mixture was cooled to -30° C., 3 ml of a solution of 635 mg(3.18 mmol) of the allyl acetate (15) obtained in example 3 (1st step)in THF was added dropwise and the mixture was stirred for one hour.After adding a saturated aqueous ammonium chloride, the mixture waswarmed to a room temperature and extracted with diethyl ether, and theextract was washed with a saturated aqueous sodium bicarbonate and thenwith brine. The solution was dried on anhydrous magnesium sulfate andconcentrated under reduced pressure, and 1.05 g of crude acetonide wasobtained as a residue. A mixture of 830 mg of crude acetonide, 2 ml of5% hydrochloric acid and 5 ml of methanol was stirred at roomtemperature for 3 hours. The mixture was neutralized with sodiumbicarbonate and concentrated under reduced pressure, and the residue wasdissolved in dichloromethane. The solution was dried on anhydrousmagnesium sulfate, and concentrated under reduced pressure. The residuewas purified by silica gel chromatography and 335 mg (74%) of the1-phenyl-4, 5-dihydroxy-2pentene represented by the formula (1d) wasobtained.

[α]_(D) ²⁷ +9.9°(c 1.03, CHC1₃),

IR (neat):3360cm⁻¹,

¹ H-NMR δ:7.40-710(m, 5H), 5.95(td, 1H, J=5.3, 16.0Hz), 5.50(dd, 1H,J=5.0,16.0hz), 4.30-4.05(m,1H), 3.80-3.30(m, 2H), 3.45(d, 2H, J=6.6Hz),2.20-1.80(m, 2H),

MS m/e:178, 147, 129.

2nd step

To a suspension of 800mg of ground molecular sieves 4A (MS-4A) in 15 mlof dichloromethane, a solution of 0.44 ml (1.47 mmol) of titaniumtetraisopropoxide, and 395 mg (1.68 mmol) of L-(+)-DIPT in 3 ml ofdichloromethane was added, and the mixture was stirred for 30 minutes.After adding a solution of 250 mg (1.4 mmol) of 1-phenyl-4,5-dihydroxy-2-pentene represented by the formula (1d) obtained in (1stStep) in 3 ml of dichloromethane, the mixture was stirred for one hour,and 1.2 ml (2.1 mmol) of a 1.8M-TBHP dichloromethane solution was addeddropwise, and the mixture was stirred at -20° C. for 72 hours. 3 ml ofwater and 15 ml of acetone were added to the mixture, and the mixturewas stirred at room temperature and filtered with cerite, and then thefiltrate was concentrated. The residue was purified by silica gelchromatography and 236 mg (87%) of 1-phenyl-4, 5-dihydroxy-2,3-epoxypentane represented by the formula (6) was obtained.

[α]_(D) ²⁷ -13.3°(c 1.01, CHC1₃),

IR (neat):3460, 1608cm⁻¹,

¹ H-NMR δ:7.40-7.10(m, 5H), 3.80-3.50(m, 3H), 3.25-3.18(m, 1H),2.95-2.90(m, 1H), 2.90-2.85(m, 2H), 2.80(brs, 1H), 2.50(brs, 1H),

MS m/e:194, 163.

EXAMPLE 5 ##STR25##

Production of the optically active epoxide represented by the formula(7) (a compound in the formula (2) wherein R is a 1-pentenyl group).

1st step

4.8 ml (6.3 mmol) of a solution of 1.32M-pentenyl magnesium bromide inTHF was added dropwise to a solution of 600 mg (3.15 mmol) of copper (I)iodide in 10 ml of THF at -30° C. and the mixture was stirred at 0° C.for 15 minutes. The mixture was cooled to -30° C., a solution of 300 mg(2.1 mmol) of the chloride (14) obtained in (1st Step) of Example 2 in 3ml of THF was added dropwise, and the mixture was stirred for 1 hour.After adding a saturated aqueous ammonium chloride to the mixture, themixture was warmed to room temperature and extracted with diethyl ether.The extract was washed with a saturated aqueous sodium bicarbonate andwith brine. The solution was dried on anhydrous magnesium sulfate andconcentrated under reduced pressure to obtain 344 mg (78%) of crudeacetonide as a residue. A mixture of 310 mg of crude acetonide, 3 ml of5% hydrochloric acid and 5 ml of methanol was stirred for 3 hours atroom temperature. After neutralizing with sodium bicarbonate, themixture was concentrated under reduced pressure, and the residue wasdissolved in dichloromethane. The solution was dried on anhydrousmagnesium sulfate and concentrated under reduced pressure. The residuewas purified by silica gel chromatography and 230 mg (92%) of the1,2-dihydroxy-3,9-decadiene represented by the formula (1e) wasobtained.

[α]_(D) ²⁶ +15.4°(c 1.06, CHC1₃),

IR (neat):3340, 1640, 1075cm⁻¹,

¹ H-NMR δ:6.05-4.80(m, 5H), 4.30-4.00(m, 1H), 3.75-3.30(m, 2H),2.31-1.80(brm, 6H), 1.50-1.30(brm, 4H),

MS m/e:169, 139, 57.

2nd Step

A solution of 0.36 ml (1.20 mmol) of titanium tetraisopropoxide and 320mg (1.37 mmol) of L-(+)-DIPT in 3 ml of dichloromethane was added to asuspension of 600 mg of ground dry molecular sieves 4A (MS-4A) in 15 mlof dichloromethane, and the mixture was stirred for 30 minutes. Afteradding a solution of 195 mg (1.14 mmol) of 1,2-dihydroxy-3,9-decadienerepresented by the formula (1e) obtained in (1st Step) in 3 ml ofdichloromethane, the mixture was stirred for 1 hour. 0.96 ml (1.72 mmol)of 1.8M-TBHP dichloromethane solution was added dropwise to the mixtureand the mixture was stirred at -20° C. for 72 hours. After adding 3 mlof water and 5 ml of acetone, the mixture was stirred at roomtemperature and filtered with cerite, and then the filtrate wasconcentrated. The residue was purified by silica gel chromotography and116 mg (56%) of 1,2-hydroxy-3,4-epoxy-9-decene represented by theformula (7) was obtained.

[α]_(D) ²⁶ +15.4°(c 1.06, CHC1₃),

IR (neat):3390, 1641cm⁻¹,

¹ H-NMRδ:6.10-5.50(m, 1H), 5.10-4.80 (m, 2H), 3.70-3.50(brs, 3H),3.40(brs, 1H), 3.15(brs, 1H), 3.00-2.70(m,2H), 2.20-1.90(brm,2H),1.70-1.15(brm,6H),

MS m/e:187, 95, 67.

EXAMPLE 6 ##STR26##

Production of the optically active epoxide represented by the formula(8) (a compound of the formula (2) wherein R is a tetradecyl group)

1st Step

A solution of 11.9 ml (8.31 mmol) of 0.7M-tetradecyl magnesium bromidein THF was added dropwise to a solution of 791 mg (4.15 mmol) of copper(I) iodide in 15 ml of THF, and the mixture was stirred at 0° C. for 15minutes. The mixture was cooled to -30° C. A solution of 400 mg (2.77mmol) of the chloride represented by the formula (14) obtained in (1stStep) of Example 2 in 3 ml of THF was added dropwise to the mixture, themixture was stirred for 1 hour. After adding a saturated aqueousammonium chloride, the mixture was warmed to room temperature andextracted with diethyl ether. The extract was washed with a saturatedaqueous sodium bicarbonate and with brine. The solution was dried onanhydrous magnesium sulfate, and concentrated under reduced pressure.The residue was purified by silica gel chromatography and 490 mg (88%)of the dihydroxy compound represented by the formula (1f) was obtained.

[α]_(D) ²⁷ +9.2°(c 1.03, CHC1₃),

¹ H-NMR δ:5.85(td, 1H, J=5.4, 16.0Hz), 5.45(dd, 1H, J=5.0, 16.0Hz),4.40-4.10(m, 1H), 3.85-3.30(m, 2H), 2.10-1.80(m, 4H), 1.70-1.20(brm,4H), 1.26(brs, 22H), 0.80(brt, 3H, J=7.3Hz).

2nd Step

To a suspension of 800 mg of ground dry molecular sieves 4a (MS-4a) in30 ml of dichloromethane, a solution of 0.47 ml (1.58 mmol) of titaniumtetra isopropoxide, 408 mg (1.73 mmol) of L-(+)-DIPT in 3 ml ofdichloromethane was added at -20° C., and the mixture was stirred for 30minutes. A solution of 330 mg (1.44 mmol) of the dihydroxy compoundrepresented by the formula (1f) obtained in (1st Step) was added to themixture, the mixture was stirred for 1 hour. After 0.96 ml (1.73 mmol)of 1.8M-TBHP dichloromethane solution was added dropwise, the mixturewas stirred at -20° C. for 72 hours. After adding 3 ml of water and 15ml of acetone, the mixture was stirred at room temperature and filteredwith cerite, and then the filtrate was concentrated. The residue waspurified by silica gel chromatography and 223 mg (63%) of the dihydroxyepoxide represented by the formula (8) was obtained.

[α]_(D) ²⁸ -20°(c 0.98, CHC1₃),

IR (neat):3340cm⁻¹,

¹ H-NMRδ:3.70(brs, 3H), 3.20-2.65(brm, 5H), 1.70-1.20(brm,4H), 1.26(brs,26Hz), 0.80(brt, 3H,J=7.3Hz),

MS m/e:282, 267, 57.

3rd Step

To a mixture of 140 mg (0.57 mmol) of the dihydroxyepoxide representedby the formula (8) obtained in (2nd Step), 1 ml of a saturated aqueoussodium bicarbonate, 1 ml of water, 2 ml of methanol and 2 ml of THF, onice cooling 246 mg (1.14 mmol) of sodium periodide was added. After themixture was stirred for 3 hours, 65 mg (1.71 mmol) of sodium borohydridewas added, and the mixture was stirred for 30 minutes. The reactionmixture was extracted with dichloromethane, and the extract was dried onanhydrous sodium sulfate and concentrated under reduced pressure. Theresidue was purified by silica gel chromatography and 110mg (91%) of thehydroxyepoxide represented by the formula (18f) was obtained. Theanalytical results of ¹ H-NMR were agreed very closely with those ofreference values. Further, compared with the optical rotation ofreference value, it was found that the hydroxyepoxide represented by theformula (18f) was substantially optically pure.

[α]_(D) ²⁶ -22.5°(c 1.00, CHC1₃), (Reference value, enantiomer [δ]_(D)²³ +22.5°(c 0.79, CHC1₃),

W. R. Roush et at., J. Org. Chem., 50, 3752(1985)).

The process of the present invention is an excellent method forproducing chiral epoxides, by which the steric configuration of threeasymmetric positions can be fully controlled. Further, the reaction canbe conducted under mild conditions, and the chemical yields and opticalyields are very high. In addition, since the substrate specificity islow, as shown in Table 1 as embodiments, substrates having severalconstitutions can be used as starting materials to produce correspondingchiral epoxides.

Further, according to the process of the present invention, it ispossible to produce the optically active epoxide represented by theformula (22) having high optical purity. The above intermediaterepresented by the formula (9) for synthesizing leukotriene can beobtained by the reduction of the resulting compound (22) with a Lindlarcatalyst. ##STR27##

Similarly, the compound represented by the formula (23) which isobtained by the process of the present invention can be introduced tothe intermediate represented by said formula (10) for synthesizingleukotriene via steps of hydroboration and oxidation reactions.##STR28##

Moreover, optically active compounds which can be efficiently producedby the process of the present invention are available as startingmaterials of several kind of useful compounds. ##STR29##

For example, from the compound of Example 1, the compound represented bythe formula (20) from which D-arabinitol is induced by a known reaction,is induced by a process of protection of two hydroxy groups, epoxidering opening and debenzylation. (T. Katsuki et al., J. Org. Chem., 47,1371 (1982)).

Moreover, by using a compound having a steric configuration differentfrom that of the compound represented by the formula (3), correspondingseveral kind of saccharides, ribitol and xylitol can be prepared insteadof the compound represented by the formula (21).

We claim:
 1. A process for the production of an optically active epoxiderepresented by the general formula: ##STR30## wherein R is a hydrocarbongroup of 40 or less carbon atoms and it may contain at least an oxygen,a nitrogen or a sulfur, which comprises reacting an alkenyl ethyleneglycol represented by the general formula: ##STR31## wherein R is thesame as that described above, with 0.5 to 2.0 equivalents of atitanium-tetraalkoxyde, a peroxide and an L-(+)- or D-(-)-dialkyltartrate at a temperature of -78°to 50° C. to asymmetrically oxidize thealkenyl ethylene glycol.
 2. A process according to claim 1 wherein thetitanium teraalkoxyde is titanium tetraisopropoxide.
 3. A processaccording to claim 1 wherein the peroxide is t-butylhydroperoxide.
 4. Aprocess according to claim 1 wherein the dialkyl tartrate is diisopropyltartrate.